Purinergic Receptor Nanoimmunoamplifiers Potentiate Chemoimmunotherapy Efficacy in Hepatocellular Carcinoma.

ABSTRACT: The effectiveness of chemoimmunotherapy for hepatocellular carcinoma (HCC) is hindered by the weak immunogenicity of chemotherapy-induced immunogenic cell death (ICD). This limitation primarily stems from the insufficient activation of the extracellular adenosine triphosphate (eATP)/P2X7 purinergic receptor (P2X7R)/NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome pathway in dendritic cells (DCs). To address this challenge, we designed ivermectin-MnO₂ nanocomplexes (IMNs) as P2X7R-targeted nanoimmunoamplifiers to enhance the immunogenicity of chemotherapy-induced ICD. The ivermectin component of IMN enhanced liposomal doxorubicin (LD)-induced ICD and increased P2X7R sensitivity to eATP. Additionally, the MnO₂ component of IMN alleviated tumor hypo

SUBMITTER: Zhang J 

PROVIDER: S-EPMC12590479 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature